Department of Drugs and Medicines, Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, Brazil.
Drug Dev Ind Pharm. 2021 Dec;47(12):1904-1914. doi: 10.1080/03639045.2022.2048664. Epub 2022 May 26.
Nanostructured polyelectrolyte complexes (nano PECs) were obtained by polyelectrolyte complexation technique from chitosan (CS) and sodium alginate (SA). Different polymer proportions were tested, as well as the addition order and homogenization type, to assess the influence on the nano PECs characteristics. The spherical shape and nanometric scale of the systems were observed by scanning electron microscopy (SEM). Nano PECs size, PDI, and zeta potential (ZP) ranged from 252 to 616 nm, from 0.22 to 0.73 and -50 to 30 mV, respectively. The increase of polymer proportion and the ultra-turrax homogenization led to the enlargement of particles size and PDI. However, no influence was observed on the ZP. The NP1s-Rb and NP4s-Rb, obtained through the sonicator with rifampicin (RIF) added before the CS and SA complexation, were selected due to the most promising characteristics of diameter (301 and 402 nm), PDI (0.27 and 0.26), and RIF incorporation (78 and 69%). The release profiles of RIF incorporated in both nano PECs were similar, with a sustained release of the drug for 180 min in phosphate buffer pH 7.2. The Weibull and the Korsmeyer-Peppas models better describe the RIF release from NP1s-Rb and NP4s-Rb, respectively, demonstrating that the release process was driven by different mechanism according to the particle composition. The nano PECs were lyophilized to prolong it stability and for possible nebulization. The addition of dextrose to the system allowed for resuspension after lyophilization. Therefore, with the results obtained, the incorporation of RIF in nano PECs based on CS and SA presents a promising system for the treatment of tuberculosis.
纳米聚电解质复合物(nano PECs)是通过聚电解质络合技术从壳聚糖(CS)和海藻酸钠(SA)中获得的。测试了不同的聚合物比例,以及添加顺序和均化类型,以评估它们对 nano PECs 特性的影响。通过扫描电子显微镜(SEM)观察到系统的球形形状和纳米级规模。纳米 PECs 的粒径、PDI 和 Zeta 电位(ZP)分别为 252 至 616nm、0.22 至 0.73 和-50 至 30mV。聚合物比例的增加和超高速均质化导致颗粒粒径和 PDI 的增大。然而,ZP 没有受到影响。由于直径(301nm 和 402nm)、PDI(0.27 和 0.26)和 RIF 掺入率(78%和 69%)最有希望,因此选择了通过加入利福平(RIF)的超声处理器预先进行 CS 和 SA 络合得到的 NP1s-Rb 和 NP4s-Rb。两种纳米 PECs 中 RIF 的释放曲线相似,在 pH7.2 的磷酸盐缓冲液中 180min 内药物持续释放。Weibull 和 Korsmeyer-Peppas 模型分别更好地描述了 NP1s-Rb 和 NP4s-Rb 中 RIF 的释放,表明根据颗粒组成,释放过程由不同的机制驱动。纳米 PECs 经冷冻干燥以延长其稳定性,并可能进行雾化。在系统中添加葡萄糖可在冷冻干燥后重新悬浮。因此,根据获得的结果,将 RIF 掺入基于 CS 和 SA 的纳米 PECs 为治疗结核病提供了一种有前途的系统。